Development of novel synthetic serine-protease inhibitors to reduce postoperative blood loss after cardiac surgery: First experimental results

Aims: The non-specific serine-protease inhibitor aprotinin is used to reduce perioperative blood loss after cardiopulmonary bypass. Because of allergic and infectious risk and clinical side effets substitutes of aprotinin would be highly preferable. We investigated the efficacy of the novel synthetic serine-protease inhibitors CU2010 and CU2020 on blood loss in a canine model. Methods: 37 dogs were divided into five groups: control (n=5), aprotinin (n=8; Hammersmith scheme), CU2010 I. (n=8, 1,6mg/kg Hammersmith scheme) CU2010 II. (n=8, 1,6mg/kg continuous infusion) and CU2020 (n=8, 4,98mg/kg, Hammersmith scheme). All animals underwent 90-minute cardiopulmonary bypass. Endpoints were blood loss during the first two hours after application of protamin (T100-T220), activated clotting time (ACT), partial thromboplastin time (PTT), normalized prothrombin time (Quick). Results: CU2010 and CU2020 significantly reduced blood loss comparable to aprotinin ( Fig. 1 , *p<0.05). Fig. 1 While ACT and PTT normalized after protamine in the control, aprotinin and CU2010 I. groups they remained elevated in the CU2010 II. and CU2020 groups. Quick values did not differ beween the groups. Fig. 2 Conclusions: The novel serine-protease inhibitors CU2010 and CU2020 significantly reduce blood loss after cardiac surgery comparable to aprotinin. Furthermore, an additional anti-thrombotic protective effect is implicated by prolonged PTT and ACT values.